A virus-neutralising antibody is not cytotoxic in vitro

Hybridoma cell lines are characterized by a preferential loss of the heavy chain gene. This observation has led to the theory that the immunoglobulin heavy chain possesses an intrinsic cytotoxic activity in some cell types. We have generated transgenic mice expressing the heavy and light chain genes of the virus-neutralising antibody A1 carrying constant domains of the human γ1 and κ isotype. Heavy chain and light chain transgenes were under trancriptional control of identical promoter regions derived from the mammary gland specific ovine beta-lactoglobulin gene. The copy number of the heavy chain transgene was consistently lower than the copy number of the light chain gene in all lines of transgenic mice. Moreover, the light chain gene was expressed in significant excess of the heavy chain gene in the lactating mammary gland in all transgenic lines. In several transgenic lines, the differences in antibody expression were greater than could be explained by the differences in transgene copy number. One potential cause of this phenotype could be a cytotoxic effect of free heavy chain protein in embryonic cells (resulting in differences in copy number) or mammary epithelial cells (resulting in differences in transgene expression). We therefore directly assessed the effect of the expression of free A1 heavy chain protein in epithelial cell lines and in murine embryonic stem cells. However, full-length A1 heavy chain mRNA and protein could be expressed transiently and stably in both epithelial and embryonic stem cells and had no detectable effect on cell viability. Taken together, these findings argue against an inherent cytotoxicity of the free A1 heavy chain protein in epithelial or embryonic cells.